The goals of the proposed research are to examine in some detail the effects of protein calorie malnutrition on the mechanism of protection against, or pathogenesis or rotavirus infection in a mouse model. These studies will use two basic approaches: 1) investigation of virus infection at the cellular level in isolated susceptible villus enterocytes, and 2) study of the natural history of infection in malnourished and normal animals after induced infection in vivo. The role of the immune system, both humoral and cellular, in protecting the animals will be assessed. The course of rotavirus infection, including virus penetration and establishment of replication will be compared in normal and malnourished mice. A simultaneous assessment of the clinical disease will be made and correlated with replicative events. The kinetics and characterization of recovery from infection will be delineated in normal mice of different ages and in altered nutritional states. The information acquired from these experiments should provide a better understanding of the synergism of malnutrition and rotaviral diarrhea. In addition, these studies should contribute to the understanding of basic pathogenic mechanisms including the development of the immune response to this virus.